By Justin Petrone
The National Institutes of Health recently awarded Biolog $923,000 to help it develop a next-generation version of the firm's cell array technology. The grant, called "Phenotype microarray analysis of fastidious pathogens," was awarded under the American Recovery and Reinvestment Act of 2009.
CEO Barry Bochner told BioArray News last week that Biolog will use the funds to continue adapting its Phenotype Microarray platform to study Mycobacterium tuberculosis and other fastidious pathogens, expand its Microbial Identification System to cover more fastidious species, and work with researchers at Texas A&M University to study gene function in Mycobacterium.
Biolog's Phenotype Microarray platform is currently used to study the physiological and metabolic properties of a wide range of microbial cells, according to the grant abstract. Using the PM platform, researchers can scan nearly 2,000 phenotypes of a microbial cell line in a single experiment.
However, a number of fastidious genera are currently not amenable to PM analysis because they are difficult to culture. Biolog intends to enhance its PM technology to study agents of lung, cutaneous, and tissue infections such as Mycobacterium, Nocardia and Legionella; microaerophilic gastrointestinal pathogens, including Helicobacter, Campylobacter, and Wolinella; and colonizers of the colon and vagina, such as Bacteroides, Clostridium, and Escherichia, according to the abstract.
"Part of this has to do with our customer base doing basic research to understand the properties of bacteria that grow on and in the human body," Bochner said of the project. According to Bochner, the new work is being funded to assist the NIH's Human Microbiome Project, part of its Roadmap for Medical Research that funds various studies to determine how microbial cells impact human health.
"The NIH has recognized the importance of understanding the basic biology of these microorganisms and their interaction with the human host," he said. "Biolog technology is being funded in recognition of the utility of our PM testing platform."
As part of that effort, Biolog will seek to lower the cost and increase the throughput of its existing PM platform by developing a new plastic microfluidic device. "This is would be a miniaturized, microfluidic version of our current system," said Bochner. "We would like to have a better piece of hardware to make it easier to put the cells into hundreds of different wells, and we would like to bypass pipetting by developing a better device."
Bochner said Biolog's goal is to get a working prototype developed within the first year of the grant. In terms of price, Bochner added that Phenotype Microarrays currently cost anywhere from between $25 and $500, depending on the array. Biolog hopes to cut the cost of its arrays in half by developing the next-gen platform.
A further goal of Biolog's project is to expand the capabilities of its Microbial Identification System to study fastidious pathogens. Biolog's microplate-based system allows users to identify different species of aerobic and anaerobic bacteria, yeasts, and fungi.
"We want to understand how to test these bacteria so that we can add them to the capability of our GEN III species identification system," Bochner said. Biolog launched the Gen III last year. Using the system, microbiology testing labs can identify 1,044 species.
"We want to continue to push the envelope and add even more species that are important in human health," Bochner said of the project. "We have already added Nocardia, which can cause severe respiratory diseases. We also would like to add Mycobacterium and perhaps also Mycoplasma species."
A final goal of Biolog's project is to work with Texas A&M University researcher Lacy Daniels to study Mycobacterium, and use knockout strains with the PM platform to study the function of genes that are unique to the metabolism and drug resistance of the genus, Bochner said. "If successful, this aspect of the project will aid efforts toward the development of new or more effective anti-mycobacterial drug therapies," he added.
Daniels' lab at Texas A&M has expertise in Mycobacterium genetics and metabolism. "They are working to understand genes that are important and unique to making Mycobacterium such a difficult pathogen to culture and to kill as well as genes involved in antibiotic drug resistance," Bochner said. "They have already presented data on an important gene that they found, using PM technology, to be involved in trehalose metabolism."
Bochner said that Mycobacterium is "unique in having trehalose mycolates in their membrane." He said the "enzymes coded by these unique mycobacterial genes could turn out to be good antibiotic drug targets."
As Biolog's projects are focused on pathogens that affect human health, the company envisions that the projects will also aid researchers that are involved in biodefense-related projects.
"Some of the biodefense-related bacteria are difficult to culture and researchers would like to understand the properties of these cells in more detail," Bochner said. "Our customers would like to be able to understand how key genes involved in pathogenicity affect a cell. There's a substantial segment of users of our technology that get funded through biodefense initiatives, either from the NIH or the US Department of Defense."